Intraerythrocytic Plasmodium falciparum Expresses a High Affinity Facilitative Hexose Transporter

Asexual stages of Plasmodium falciparum cause severe malaria and are dependent upon host glucose for energy. We have identified a glucose transporter ofP. falciparum (PfHT1) and studied its function and expression during parasite development in vitro. PfHT1 is a saturable, sodium-independent, and st...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-03, Vol.274 (11), p.7272-7277
Main Authors: Woodrow, Charles J., Penny, Jeffrey I., Krishna, Sanjeev
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cloning, Molecular
Erythrocytes - parasitology
Female
Fluorescent Antibody Technique
Hexoses - metabolism
Molecular Sequence Data
Monosaccharide Transport Proteins - chemistry
Monosaccharide Transport Proteins - genetics
Monosaccharide Transport Proteins - metabolism
Plasmodium falciparum
Plasmodium falciparum - genetics
Plasmodium falciparum - metabolism
Protein Conformation
Protozoan Proteins
RNA, Messenger - genetics
Sequence Homology, Amino Acid
Xenopus laevis
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Summary:Asexual stages of Plasmodium falciparum cause severe malaria and are dependent upon host glucose for energy. We have identified a glucose transporter ofP. falciparum (PfHT1) and studied its function and expression during parasite development in vitro. PfHT1 is a saturable, sodium-independent, and stereospecific transporter, which is inhibited by cytochalasin B, and has a relatively high affinity for glucose (Km = 0.48 mm) when expressed in Xenopus laevis oocytes. Competition experiments with glucose analogues show that hydroxyl groups at positions C-3 and C-4 are important for ligand binding. mRNA levels for PfHT1, assessed by the quantitative technique of tandem competitive polymerase chain reaction, are highest during the small ring stages of infection and lowest in gametocytes. Confocal immunofluorescence microscopy localizes PfHT1 to the region of the parasite plasma membrane and not to host structures. These findings have implications for development of new drug targets in malaria as well as for understanding of the pathophysiology of severe infection. When hypoglycemia complicates malaria, modeling studies suggest that the high affinity of PfHT1 is likely to increase the relative proportion of glucose taken up by parasites and thereby worsen the clinical condition.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.11.7272